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Bayesian model selection for analyzing predictor-dependent directional data
Get PDFThe need for models for directional data is increasing, driven primarily by the necessity of analyzing peak hours in 24-hour services. Motivated by the need to analyze demand data for a 24-hour bike rental service in Seoul and the factors influencing demand fluctuations across distinct hours, we develop a Bayesian nonparametric density regression modeling framework for the case of a circular response and linear covariates, allowing model selection. Our proposal is based on a linear dependent Dirichlet process mixture of projected normal distributions, accommodating asymmetrical and multimodal shapes, in conjunction with discrete spike-and-slab priors, to enable model selection. A further advantage of our approach is that it enables model averaging, thereby properly accounting for model uncertainty. The simulation study shows that, across various scenarios, our model (i) successfully recovers the true functional form of the conditional density and (ii) selects the correct model, with accuracy improving as the sample size increases. The application of our method suggests that weather conditions significantly impact bike demand. The approach also allows us to predict peak rental times, revealing that, for instance, on a typical summer day, bike demand decreases between 8 am and 4 pm, while in winter, it drops during the early morning
L1 Attrition vis-à-vis L2 Acquisition:Lexicon, syntax-pragmatics Interface and prosody in L1-English L2-Italian late bilinguals
Get PDFLate bilingual speakers immersed in a second language (L2) environment often experience the non-pathological attrition of their first language (L1), exhibiting selective and reversible changes in L1 processing and production. While attrition research has largely focused on long-term residents in anglophone countries, examining changes primarily within a single L1 domain, the present study employs a novel experimental design to investigate L1 attrition, alongside L2 acquisition, across three domains (i.e., the lexicon, syntax–pragmatics interface, and prosody) in two groups of L1-English L2-Italian late bilinguals: long-term residents in Italy vs. university students in the UK. A total of 112 participants completed online tasks assessing lexical retrieval, anaphora resolution, and sentence stress patterns in both languages. First, both bilingual groups showed comparable levels of semantic interference in lexical retrieval. Second, at the syntax–pragmatics interface, only residents in Italy showed signs of L1 attrition in real-time processing of anaphora, while resolution preferences were similar between groups; in the L2, both bilingual groups demonstrated target-like preferences, despite some slowdown in processing. Third, while both groups showed some evidence of target-like L2 prosody, with residents in Italy matching L1-Italian sentence stress patterns closely, prosodic attrition was only reported for residents in Italy in exploratory analyses. Overall, this study supports the notion of L1 attrition as a natural consequence of bilingualism—one that is domain- and experience-dependent, unfolds along a continuum, and involves a complex (and possibly inverse) relationship between L1 and L2 performance that warrants further investigation
Inherited prion disease caused by a novel frameshift mutation of PRNP resulting in protein truncation at codon 157.
Get PDFBackgroundPrP systemic amyloidosis is increasingly recognized as a novel inherited prion disease (IPD) syndrome caused by PRNP C-terminal truncating mutations. As well as systemic manifestations they cause gradually progressive cognitive impairment with neurofibrillary tangle pathology which can be mistaken for Alzheimer's disease (AD).ObjectiveWe describe the clinical, biomarker and neuropathological features of a novel frameshift mutation of PRNP resulting in protein truncation at codon 157.MethodsThe clinical phenotype and biomarker findings, including plasma biomarkers measured using Single Molecule Array (SiMOA) technology are reported for affected living individuals, with neuropathological examination available for the index case.ResultsThe Y157X PRNP mutation has resulted in a phenotype of gradually progressive cognitive decline, peripheral sensory and autonomic polyneuropathy, and gastrointestinal symptoms, with one case presenting with recurrent episodes of nausea, vomiting and electrolyte derangement requiring intensive care unit admission. Plasma biomarkers revealed an AD-like pattern with raised neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and phospho-tau 181 (P-tau 181) in affected individuals. On neuropathological examination there was PrP-cerebral amyloid angiopathy (CAA) and neurofibrillary tau pathology.ConclusionsWe present the clinical, biomarker and pathological findings on investigation of this family and provide further evidence for the association of truncation mutations with PrP systemic amyloidosis. </p
Pyrolysis front tracking using the spectral fluorescence signature of PMMA
Get PDFThe ability to track the progression of a pyrolysis front on a solid fuel is essential in many applications such as the study of flame spread. Tracking the pyrolysis front in cases such as upwards flame spread becomes increasingly difficult due to the obstruction of the luminous flame. This work identifies the occurrence of light-induced fluorescence in the pyrolysis region of polymethyl methacrylate (PMMA) during flame spread and demonstrates its use in explicitly identifying the pyrolysis front. PMMA fluorescence is achieved through excitation using 266 nm, 395 nm, and 450 nm light (both coherent laser and LED sources). The fluorescence response was characterized through UV–VIS spectroscopy. Pyrolyzed PMMA excited with 266 or 395 nm light provided a fluorescence signature with a strong peak at ~532 nm and a half width of ~160 nm. The ability to visualize and track the pyrolysis region is demonstrated for both downwards and upwards flame spread. For downward spread, the onset of fluorescence was found to occur within 1 mm of the leading edge of the flame. Upward flame spread experiments demonstrated that pyrolysis fluorescence can be detected through the obscuration of the luminous flame, allowing for pyrolysis front tracking while simultaneously tracking the flame front through chemiluminescence imaging
Policies slow biological invasions in Europe, but legacies still matter
Get PDFBiological invasions are a main cause of biodiversity loss, prompting international agreements and national policies aimed at preventing and managing the introduction, establishment, spread, and impacts of alien species. However, whether these measures have effectively reduced invasions remains uncertain. In this study, we compared the absolute number of established alien species and changes in invasion rates, accounting for sampling effort and invasion timing, across European Union (EU) countries and the United Kingdom (UK) with the number and types of policies implemented. Policy effects were analyzed alongside other invasion drivers, including trade, climate, and geography. We demonstrate for the first time that invasive species policies within the EU and the UK had significant protective effects. Notably, these effects were evident only when examining changes in invasion rates, emphasizing the need to consider invasion dynamics and policy timing. These results should encourage countries to continue managing invasions and contribute to refining strategies for managing alien species.</p
The Psychiatric Genomics Consortium: discoveries and directions
Get PDFResearch by the Psychiatric Genomics Consortium (PGC) has advanced the discovery of common and rare genetic variations that contribute to the susceptibility to many psychiatric disorders and neurodevelopmental conditions. This Review reflects on major findings from the past 5 years of research by the PGC in five priority areas: discovery of common variants using genome-wide association studies; rare variation and its interplay with polygenic risk; using genetics to go beyond diagnostic boundaries; ascribing functional attributes to genomic discoveries; and developing and implementing processes for data sharing, outreach to various communities, and training. The insights gained in these domains frame the agenda for the next phase of PGC research. In addition to accelerating integrative findings of common and rare variants within, and across, multiple psychiatric disorders and neurodevelopmental conditions, the next phase will use multiple populations to elucidate genetic causes, integrate results with rapidly accumulating multimodal functional genomics data to gain mechanistic understanding, convert genetic findings to clinically actionable phenotypes, such as treatment response, and address the emerging use of polygenic scores. Together, these next steps will highlight the biological underpinnings of psychiatric disorders and neurodevelopmental conditions, which continue to contribute to global morbidity and mortality.</p
External validation of paediatric pneumonia and bronchiolitis risk scores to predict mortality in children hospitalized in Kenya:a retrospective cohort study
Get PDFBackgroundAcute lower respiratory tract infections (ALRIs) are a leading cause of paediatric mortality in low- and middle-income countries. In recent years, substantial research has been done to enhance risk stratification of children presenting with ALRIs, in a bid to improve health outcomes in resource-limited settings. We sought to analyse the performance of several paediatric ALRI risk scores in the prediction of mortality among children hospitalised with ALRIs in Kenya.MethodsWe retrospectively analysed the data of 2182 children aged 2-24 months who were admitted to Kilifi County Referral Hospital, Kenya with severe ALRIs between January 2015 and December 2024. We evaluated the performance of 6 ALRI risk scores (RISC (HIV-Negative), mRISC, RISC-Malawi, PERCH, PREPARE, ReSVinet) in this population. Additionally, we created and evaluated a modified version of the ReSVinet score by including nutrition status. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC).ResultsThe mid-upper arm circumference (MUAC) version of the RISC-Malawi score showed the highest discrimination for the outcome of in-hospital mortality (AUROC: 0.83, 95% CI: (0.79 – 0.86)), whilst all other scores showed acceptable discrimination (AUROC: 0.70 – 0.79). The modification of ReSVinet to include nutrition status significantly improved its AUROC from 0.72 to 0.79.ConclusionAll risk scores showed at least fair performance in the prediction of in-hospital mortality within our dataset. The RISC-Malawi (MUAC) score appears to be the most promising candidate for future implementation, however further research is needed to evaluate the calibration, feasibility and clinical utility of these scores.<br/
Early life high fructose impairs microglial phagocytosis and neurodevelopment
Get PDFDespite the success of fructose as a low-cost food additive, epidemiological evidence suggests that high fructose consumption during pregnancy or adolescence is associated with disrupted neurodevelopment 1, 2–3. An essential step in appropriate mammalian neurodevelopment is the phagocytic elimination of newly formed neurons by microglia, the resident professional phagocyte of the central nervous system 4. Whether high fructose consumption in early life affects microglial phagocytosis and whether this directly affects neurodevelopment remains unknown. Here we show that offspring born to female mice fed a high-fructose diet and neonates exposed to high fructose exhibit decreased phagocytic activity in vivo. Notably, deletion of the high-affinity fructose transporter GLUT5 (also known as SLC2A5) in neonatal microglia completely reversed microglia phagocytic dysfunction, suggesting that high fructose directly affects neonatal development by suppressing microglial phagocytosis. Mechanistically, we found that high-fructose treatment of mouse and human microglia suppresses phagocytosis capacity, which is rescued in GLUT5-deficient microglia. Additionally, we found that high fructose drives significant GLUT5-dependent fructose uptake and catabolism to fructose 6-phosphate, rewiring microglial metabolism towards a hypo-phagocytic state in part by enforcing mitochondrial localization of the enzyme hexokinase 2. Mice exposed to high fructose as neonates develop anxiety-like behaviour as adolescents—an effect that is rescued in GLUT5-deficient mice. Our findings provide a mechanistic explanation for the epidemiological observation that high-fructose exposure during early life is associated with increased prevalence of adolescent anxiety disorders.</p
Who considers migrants' competence important?:The role of political ideology
Get PDFEstablished theories have recognised competence as a fundamental dimension in social judgements of migrants, but it remains unclear who particularly values competence in this context. In an experimental study with British participants (N = 510), we examined how majority group members' political ideology influences their judgements about the importance of migrant competence and how migrant warmth moderates this relationship. We also tested competitive and dangerous worldviews as potential mediators of this process. The results showed that conservatives placed greater importance on migrant competence than liberals, particularly when the migrant group was described as warm. Additionally, while conservative ideology predicted a greater perceived importance of migrant competence through heightened competitive and dangerous worldviews, migrant warmth did not moderate these indirect effects. These findings enhance our understanding of when and why majority group members value migrant groups' competence and highlight the complexity of ideological motivations in intergroup judgements
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